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F F Knapp

Publications and source records attributed to F F Knapp.

At least 73 records · Page 4Linked to original sources
PubMed1997

In vivo autoradiographic competition studies of isomers of [125I]IQNP against QNB demonstrating in vivo m2 muscarinic subtype selectivity for QNB.

(R,S)-[125I]IQNB has been used extensively in in vivo studies in rats, and has been of utility in demonstrating the in vivo subtype selectivity of nonradioactive ligands in competition studies. Because of the implications for the study of Alzheimer's disease (AD), those ligands that demonstrate m2 selectivity are of particular interest. Radiolabelled Z- and E-(-,-)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z- and E-(-,-)-[125I]IQNP) are analogs of (R,S)-[125I]IQNB. Rat brain regional dissection studies and in vivo autoradiographic comparison of the time-courses of (R,S)-[125I]IQNB, Z-(-,-)-[125I]IQNP, and E-(-,-)-[125I]IQNP have indicated that Z- and E-(-,-)-[125I]IQNP, in general, are distributed similarly to (R,S)-[125I]IQNB. Z-(-,-)-[125I]IQNP binds to the muscarinic receptors in those brain regions enriched in the m2 subtype with approximately a two- to fivefold higher % dose/g compared with (R,S)-[125I]IQNB. Thus, as we show here autoradiographically, using QNB as the competing nonradioactive ligand in in vivo competition studies against Z-(-,-)-[125I]IQNP provides a sensitive and accurate probe for demonstrating the in vivo m2 selectivity of nonradioactive ligands.

Animals↗
PubMed1997

Heterogeneity of DMIPP uptake and its relationship with heterogeneous myocardial blood flow.

UNLABELLED: To assess its potential role as a new metabolic probe, the relationship between regional uptake of the 15-(p-[125I]-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP) fatty acid analog and myocardial blood flow was studied. METHODS: In 14 open-chest dogs, the left anterior descending coronary artery was cannulated and extracorporal bypass-perfused at normal (control group; n = 4) and reduced flow (intervention group; n = 10). Myocardial blood flow (MBF) was assessed with 46Sc-labeled microspheres. Forty minutes after intravenous injection of DMIPP, the heart was excised and cut into 120 samples. In each sample, MBF ml x g(-1) x min(-1) and DMIPP uptake (percentage of the injected dose per gram, %ID/g) were assessed. RESULTS: In normal myocardium, MBF and DMIPP uptake were 1.10 +/- 0.18 ml x g(-1) x min(-1) and 1.18 +/- 0.42 x 10(-2) %ID/g, respectively. In the extracorporal bypass area, flow was reduced to 0.49 +/- 0.20 ml x g(-1) x min(-1) (p < 0.0001 compared to normal), and DMIPP uptake was decreased to 0.75 +/- 0.26 x 10(-2) %ID/g (p < 0.0001 compared to normal). DMIPP uptake and MBF positively correlated in normal (DMIPP uptake = 0.77 +/- 0.23 x MBF; r = 0.41; p < 0.0001) and hypoperfused (DMIPP uptake = 0.35 +/- 0.70 x MBF; r = 0.63; p < 0.0001) myocardium. The heterogeneity, indicated by the coefficient of variation, in normal myocardium was 0.23 +/- 0.05 for MBF and was lower (p < 0.0001) for DMIPP uptake: 0.13 +/- 0.05. During flow reduction, heterogeneity increased significantly (p < 0.0001) for both MBF (0.59 +/- 0.22) and DMIPP uptake (0.37 +/- 0.23). Also heterogeneity of the DMIPP uptake to MBF ratio, as an indicator of agreement, increased from 0.23 +/- 0.07 in normal to 0.46 +/- 0.19 in hypoperfused myocardium (p < 0.0001). CONCLUSION: DMIPP detects regionally hypoperfused myocardium, in which agreement between MBF and fatty acid uptake deteriorates. DMIPP uptake shows a different relationship with MBF in hypoperfused compared to normal myocardium. These observations suggest that DMIPP uptake may provide additional, unique information on regional myocardial ischemia.

Animals↗
PubMed1997

Effects of configuration on the myocardial uptake of radioiodinated 3(R)-BMIPP and 3(S)-BMIPP in rats.

UNLABELLED: Radioiodinated 3(R)-(+)- and 3(S)-(-)-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) were prepared and evaluated in rats to investigate the effects of absolute configuration of the 3(beta)-methyl group on myocardial uptake and release kinetics. METHODS: The 3(R)-(+)-BMIPP analog was synthesized by initial acylation of a thiophene template with the acid chloride of ethyl 3(R)-methylglutarate. 3(S)-(-)-BMIPP was obtained by separation from the mixture of diastereomeric amides prepared from reaction of the acid chloride of racemic BMIPP with the S-(-)-alpha-methylbenzylamine. The amide of synthetic 3(R)-BMIPP prepared from S-(-)-alpha-methylbenzylamine was identical to the chromatographically more polar isomer. Free acids were obtained by acid hydrolysis of the amides, fully characterized and then converted to the radioiodinated BMIPP isomers. RESULTS: Biodistribution studies in rats with the dual-labeled [(131)I]-3(S)-BMIPP/[(125)I]-3(R)-BMIPP mixture demonstrated greater myocardial uptake of 3(R)-BMIPP compared with the 3(S)-BMIPP isomer [60 min: 3(R)-BMIPP = 4.37 %ID/g; 3(S)-BMIPP = 3.44; p < 0.05; 180 min, 2.31 and 1.78 %ID/G, respectively, p < 0.01], although both isomers had similar myocardial washout curves (5-180 min). Percent ID/g values for other tissues which were examined (blood, lungs, thyroid) were similar. CONCLUSION: Higher myocardial uptake of the 3(R)-BMIPP isomer observed in these animal studies may suggest differences in carrier-mediated myocyte uptake of the two isomers. These studies suggest that [(123)I]-3(R)-BMIPP is a candidate for clinical evaluation and may show greater myocardial uptake than the 3(S)-BMIPP isomer and may thus require reduced injected dose.

Animals↗
PubMed1996

Experimental radiotherapy of receptor-positive human prostate adenocarcinoma with 188Re-RC-160, a directly-radiolabeled somatostatin analogue.

The therapeutic potential of the somatostatin analogue RC-160 radiolabeled with 188Re was evaluated in nude mice bearing xenografts of human prostate adenocarcinoma. 188Re-RC-160 was selectively retained in both DU-145 and PC-3 tumors following direct intra-tumor injection at all time points examined (2, 6 and 24 hr post-injection). Unbound 188Re-RC-160 was rapidly excreted via the hepatobiliary system and, with the exception of the gastrointestinal tract, very little normal organ uptake was found at any time point examined. Negative control compounds, 188Re-perrhenate and 188Re-mercaptoacetyl-triglycine (188Re-MAG3), were essentially washed out of the tumor by 6 hr post-injection and were rapidly excreted through the kidneys. 131I-RC-160, used as reference compound, had a biodistribution in tumor-bearing animals similar to that of 188Re-RC-160. In PC-3 xenografts, 188Re-RC-160 gave a dose-dependent therapeutic response (stasis or regression) even in animals with relatively large tumor masses (greater than 600 mm3), whereas the macro-aggregated form of 188Re-RC-160 did not. Long-term studies with 188Re-RC-160 demonstrated a protracted reduction of tumor volume and a positive effect on animal survival. Neither RC-160 by itself nor a 188Re-labeled peptide, unrelated to somatostatin (PA-22-2, a laminin peptide), demonstrated the reduction in tumor mass observed with 188Re-RC-160. 188Re-RC-160 shows potential as a new clinical agent for treatment of somatostatin-receptor-positive cancers.

Adenocarcinoma↗
PubMed1996

Biodistribution of rhenium-188 Lipiodol infused via the hepatic artery of rats with hepatic tumours.

The purpose of this study was to analyse the biodistribution of rhenium-188 Lipiodol in rats with hepatic tumours following intrahepatic arterial injection to assess the potential of 188Re-Lipiodol as a radiopharmaceutical for the treatment of hepatic tumours in humans. Twelve male rats with hepatic tumours were killed at 1h, 24h and 48h after injection of approximately 7.4MBq of 188Re-Lipiodol via the hepatic artery. Samples of various organs were obtained and counted to calculate the tissue concentration. Radioactivity in the hepatic tumours was very high throughout this study, with a biological half-life of 122.9h. Radioactivity in the normal liver tissue was also high, but was significantly lower than in the tumour. The biological half-life in the normal liver tissue was 31.7h. The ratio of tumour concentration to the normal liver tissue concentration was 5.15 at 1h and rose to 7.7 at 24h and 10.84 at 48h. The level of radioactivity in the lung was high at 1h, and declined rapidly over time. The level of radioactivity in the kidney was moderate throughout the study. The radiation concentrations in muscle, spleen, testis, bone and whole blood were insignificant. We conclude that 188Re-Lipiodol should be considered as a potential radiopharmaceutical for the intra-arterial treatment of hepatic tumours.

Animals↗
PubMed1996

Both total chain length and position of dimethyl-branching effect the myocardial uptake and retention of radioiodinated analogues of 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid (DMIPP).

Introduction of geminal dimethyl-branching into the 3-position of 15-(p-iodophenyl) pentadecanoic acid (IPPA) significantly delays myocardial clearance in rats and dogs following intravenous administration. Several new analogues of DMIPP have been synthesized and evaluated in fasted rats. The effects of both the position of dimethyl-branching and the total chain-length of 3, 3-dimethyl analogues on heart uptake and clearance kinetics have been studied. In the first series of compounds, two methyl groups were introduced into the 3-, 4-, 6-, or 9- position. Tissue distribution studies of the 15-(p-[I-125] iodophenyl)-analogues demonstrated that the position of dimethyl-branching is an important factor affecting both myocardial specificity and retention. The [I-125] labeled 3,3- and 4,4-DMIPP analogues showed higher myocardial uptake and faster blood clearance than the 6,6- and 9,9-DMIPP analogues [heart, % dose/gm heart: blood), 30 min: 3,3-DMIPP = 5.06 (12:1); 4,4-DMIPP = 8.03 (16.7: 1); 6,6-DMIPP = 2.26 (3.1:1); 9,9-DMIPP = 3.06 (2.77)]. In the second series, the effects of total fatty acid chain length were evaluated with 3,3-dimethyl-substituted analogues with C11, C12, C13, C14, C15, and C19 chain lengths. The C14 and C15 chain length analogues showed the best properties [global heart: blood ratios): 30 min: C11, 0.70 (0.82); C12, 1.25 (0.68); C13, 0.47 (0.90); C14, 1.63 (3.54); C15, 5.06 (12); C19. 1.29 (0.82). These detailed studies have demonstrated that both total chain length and the position of geminal dimethyl-branching are important structural parameters which affect myocardial specificity and retention of omega-(p-iodophenyl)-substituted fatty acid analogues and that 3,3-DMIPP and 4,4-DMIPP are the best candidates with optimal properties for further study.

Animals↗
PubMed1996

Re-188 labelled antibodies.

Monoclonal antibodies can be directly labelled with 188Re using a simple one-step radiolabelling kit. Using B72.3 as a model antibody, the formulation was optimized and kits were made and tested and compared to data previously reported for the same antibody labelled with other radioisotopes. Labelling with Re-188 was carried out with the eluate of a W-188/Re-188 generator from Oak Ridge National Laboratory. Fresh generator eluate was added to the pre-reduced lyophilized antibody and the mixture allowed to incubate overnight at room temperature. The radiochemical purity, immunoreactive fraction, and biodistribution in normal and LS174T tumor bearing nude mice was determined. The radiochemical purity was 88 +/- 7%, the immunoreactive fraction was 68.46 +/- 3.8%. The immunoreactive fraction was higher than any previously reported for this antibody when labelled with other radioisotopes. At 48 h, 7.9 +/- 2.4% of the injected dose per gram was found in the tumor. The biodistribution and tumor uptake of Re-188 labelled B72.3 was similar to that previously reported for Re-186 and In-111 labelled B72.3.

Animals↗
PubMed1996

Radiolabelling of Lipiodol with generator-produced 188Re for hepatic tumor therapy.

In this study we prepared and analyzed the biodistribution of 188Re-labelled Lipiodol ([188Re]-Lipiodol) in rats after intrahepatic arterial injection. EDTB was synthesized by condensation of 1,2-benzenediamine and ethylenediaminetetraacetic acid (EDTA). The labelling efficiency of [188Re] Lipiodol was determined to be greater than 97% by ITLC developed with n-hexane. Following incubation of the [188Re] Lipiodol with an equal volume of serum at 37 degrees C for 48 h, ITLC indicated good in vitro stability. Approximately 7.4 MBq [188Re] Lipiodol was injected in each rat via the hepatic artery and samples of liver, spleen, muscle, lung, kidney, bone, whole blood and testis were obtained. [188Re] Lipiodol tissue concentrations showed that after 1 h intrahepatic injection most of the radiotracer was retained in the liver, and was eliminated slowly with a biological half-life of 33.5 h. Radioactvity levels in the lung, kidney and blood were moderate at 1 h, and declined rapidly over time. In the spleen, muscle, testis and bone, radiation levels were insignificant. These initial results indicate that -188Re- Lipiodol may be a potential radiopharmaceutical agent for the treatment of liver tumors.

Animals↗
PubMed1996

Evaluation of 1-azabicyclo[2.2.2]oct-3-yl alpha-fluoroalkyl-alpha-hydroxy-alpha-phenylacetates as potential ligands for the study of muscarinic receptor density by positron emission tomography.

Both 1-azabicyclo[2.2.2]oct-3-yl alpha-(1-fluoroeth-2-yl)-alpha-hydroxy-alpha-phenylacetate (FQNE, 5) and 1-azabicyclo[2.2.2]oct-3-yl alpha-(1-fluoropent-5-yl)-alpha-hydroxy-alpha-phenylacetate (FQNPe, 6) were prepared and evaluated as potential candidates for the determination of muscarinic cholinergic receptor (mAChR) density by positron emission tomography (PET). The results of in vitro binding assays demonstrated that although both 5 and 6 had high binding affinities for m1 and m2 mAChR subtypes, 6 displayed a higher affinity (nM, m1; KD, 0.45, m2; KD, 3.53) as compared to 5 (nM, m1; KD, 12.5, m2; KD, 62.8). It was observed that pretreatment of female Fisher rats with either 5 or 6 prior to the i.v. administration of Z-(-)(-)-[131I]-IQNP, a high-affinity muscarinic ligand, significantly blocked the uptake of radioactivity in the brain and heart measured 3 h postinjection of the radiolabeled ligand. These new fluoro QNB analogues represent important target ligands for evaluation as potential receptor imaging agents in conjunction with PET.

Animals↗
PubMed1996

Localization of small-cell lung cancer xenografts with iodine-125-, indium-111-, and rhenium-188-somatostatin analogs.

We examined the potential of radiolabeled somatostatin analogs, 125I-Tyr-3-octreotide (125I-octreotide), (111)In-DTPA(diethylenetriaminepentaacetatic acid)-D-Phe-1-octreotide (111In-octreotide), and 188Re-octreotide for targeting small-cell lung cancer (SCLC) in a mouse model. Tyr-3-octreotide was labeled with 125I by the chloramine T method, and (111)In-octreotide was obtained as a kit, while 188Re was eluted from a 188W/188Re generator, and octreotide was directly labeled with 188Re by reducing disulfide bonds. The 125I-, 111In-, and 188Re-octreotides were injected i.v. into athymic mice bearing NCI-H69 tumors, and the biodistributions were determined at 15 min, and 2, 4, 8, and 24 h. Tumor uptakes were 0.5+/-0.2, 0.3+/-0.1, 0.3+/-0.1 %ID/g, and tumor-to-blood ratios were 1.8, 11.9, 1.2 at 8 h for 125I-, 111In-, and 188Re-octreotides, respectively. Accumulations of 111In-octreotide in normal tissues were lower than those of 125I- and 188Re-octreotides. 188Re-octreotide can be used to localize SCLC lesions as efficiently as radioiodinated octreotide. However, 111In-octreotide was the most suitable agent to obtain high tumor-to-normal tissue contrast for localizing SCLC.

Animals↗
PubMed1996

In vivo autoradiographic and dissection evaluation of isomers of 125I-labeled 1-azabicyclo[2.2.2] oct-3-yl-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IQNP).

(R,S)-[125I]IQNB has been used extensively in in vivo studies in rats and has been of utility in demonstrating the in vivo subtype selectivity of nonradioactive ligands in competition studies. Radiolabeled Z- and E-(-,-)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z- and E-[-,-]-[125I]IQNP) are analogs of (R,S)-[125I]IQNB. Preliminary rat brain regional dissection studies have indicated that Z- and E-(-,-)-[125I]IQNP, in general, are distributed similarly to (R,S)-[125I]IQNB. An important observation is that Z-(-,-)-[125I]IQNP binds to the muscarinic receptors in those brain regions enriched in the m2 subtype with approximately a two- to fivefold higher percent dose/g compared to (R,S)-[125I]IQNB. These observations are confirmed here by in vivo autoradiographic comparison of the time-courses of (R,S)-[125I]IQNB, Z-(-,-)-[125I]IQNP, and E-(-,-)-[125I]IQNP. Thus, in vivo competition studies against Z-(-,-)-[125I]IQNP would provide a potentially more sensitive and accurate probe for demonstrating the in vivo m2 selectivity of the nonradioactive ligands. In addition, Z-(-,-)-[123I]IQNP would potentially be useful for SPECT imaging of muscarinic receptor loss in neurodegenerative diseases.

Animals↗
PubMed1996

Pharmacokinetics of radioiodinated fatty acid myocardial imaging agents in animal models and human studies.

Since the oxidation of long chain fatty acids is the major pathway for energy production for the normoxic myocardium, the use of radiolabeled fatty acids for myocardial imaging continues to be a major area of both basic and clinical research. This paper focuses on a discussion of the kinetics of myocardial uptake of radioiodinated fatty acids, including planar and SPECT imaging of various iodine-123-labeled analogues, and data from animal and isolated heart studies, and where possible, comparison with results of clinical studies. Key examples include iodoalkyl-substituted straight chain fatty acids such as 17-IHDA (17-iodoheptadecanoic acid). These analogues are rapidly metabolized in the myocardium, resulting in release of free radioiodide, and can only be practically used for planar imaging. Terminal iodophenyl-substituted fatty acids illustrate a successful approach of stabilizing radioiodine to overcome the release of free iodide encountered with the straight-chain analogues. These analogues, exemplified by p-IPPA [15-(p-iodophenyl)pentadecanoic acid], are widely used in clinical practice. Although washout can be delayed by increase in the arterial lactate levels by mild exercise, SPECT imaging must still be carefully timed. In contrast to these examples, the ortho iodide-substituted IPPA isomer (ortho- instead of para-phenyl substitution of radioiodide) is a unique example which shows rapid myocardial washout in laboratory animals but nearly irreversible retention in humans. Introduction of methyl-branching is a major important approach which has been successfully used to alter tracer kinetics of radioiodinated fatty acids by increasing myocardial retention. A key example in this class of compounds is 3-(R,S)-BMIPP [15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid], an analogue of p-IPPA in which methyl-branching has been introduced into the beta-position of the carbon chain. Although tracer washout is significantly delayed with this structural perturbation, a large number of clinical studies have shown that slow myocardial washout is still observed. Detailed biochemical studies with radioiodinated 3-BMIPP have demonstrated that initial alpha-oxidation produces a metabolite that can then be catabolized by alpha-oxidation. An unexpected and important observation with the (123I]-3-(R,S)-BMIPP agent has been the mis-match between perfusion tracer distribution and the regional BMIPP distribution which has been widely observed in jeopardized, but viable myocardial regions. Another example in the methyl-branched series is DMIPP [15-(p-iodophenyl)- 3,3-dimethylpentadecanoic acid], which has very prolonged myocardial retention and slow washout kinetics although only animal studies have been reported with this agent. Still another more recent approach has been the synthesis and laboratory animal and human evaluation of analogues containing a phenylene bridge in the fatty acid chain. One example is 3-10 [13-(4'-iodophenyl)]-3-(p-phenylene)tridecanoic acid (PHIPA 3-10), which has also proven successful in delaying myocardial tracer washout. This paper focuses on a discussion of the effects of molecular structure on the myocardial uptake and release of these various radioiodinated fatty acid analogues.

Animals↗
PubMed1995

Resolution and in vitro and initial in vivo evaluation of isomers of iodine-125-labeled 1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate: a high-affinity ligand for the muscarinic receptor.

1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)- alpha-phenylacetate (IQNP, 1), is a highly selective ligand for the muscarinic acetylcholinergic receptor (mAChR). There are eight stereoisomers in the racemic mixture. The optical isomers of alpha-hydroxy-alpha-phenyl-alpha-(1-propyn-3-yl)acetic acid were resolved as the alpha-methylbenzylamine salts, and the optical isomers of 3-quinuclidinol were resolved as the tartrate salts. The E and Z isomers were prepared by varying the reaction conditions for the stannylation of the triple bond followed by purification utilizing flash column chromatography. In vitro binding assay of the four stereoisomers containing the (R)-(-)-3-quinuclidinyl ester demonstrated that each isomer of 1 bound to mAChR with high affinity. In addition, (E)-(-)-(-)-IQNP demonstrated the highest receptor subtype specificity between the m1 molecular subtype (KD, nM, 0.383 +/- 0.102) and the m2 molecular subtype (29.6 +/- 9.70). In vivo biodistribution studies demonstrated that iodine-125-labeled (E)-(-)-(+)-1 cleared rapidly from the brain and heart. In contrast, iodine-125-labeled (E)-(-)-(-)-, (Z)-(-)-(-)-, and (Z)-(-)-(+)-1 have high uptake and retention in mAChR rich areas of the brain. It was also observed that (E)-(-)-(-)-IQNP demonstrated an apparent subtype selectivity in vivo with retention in M1 (m1, m4) mAChR areas of the rain. In addition, (Z)-(-)-(-)-IQNP also demonstrated significant uptake in tissues containing the M2 (m2) mAChR subtype. These results demonstrate that the iodine-123-labeled analogues of the (E)-(-)-(-)- and (Z)-(-)-(-)-IQNP isomers are attractive candidates for single-photon emission-computed tomographic imaging of cerebral and cardiac mAChR receptor densities.

Animals↗
PubMed1995

Rhenium-188 sulphur colloid as a radiation synovectomy agent.

Radiation synovectomy has been shown to be an effective treatment for the rheumatoid arthritic knee. In this study, we evaluated the suitability of rhenium-188 as a radiation synovectomy agent. In addition, we were successful in labelling sulphur colloid with 188Re. In vitro stability tests revealed that more than 95% of the 188Re remained in colloid form over a 3-day period. Intra-articular injection of 188Re sulphur colloid into arthritic rabbit joints was followed by gamma camera imaging to quantify the leakage. The mean retention percentages of 188Re colloid in arthritic knees were 93.7% (+/- 1.4%), 90.8% (+/- 1.7%) and 87.2% (+/- 0.6%) at 1 h, 1 day and 2 days, respectively. A biodistribution study of the arthritic rabbits revealed that the highest activity outside the knees was in the liver and the kidneys. Our preliminary results indicate that 188Re sulphur colloid may be an effective radiopharmaceutical for radiation synovectomy.

Animals↗
PubMed1995

Iodine-123-labelled fatty acids for myocardial single-photon emission tomography: current status and future perspectives.

Renewed interest in the clinical use of iodine-123-labelled fatty acids is currently primarily focused on the use of iodine-123-labelled 15-(p-iodophenyl)pentadecanoic acid (IPPA) and "modified" fatty acid analogues such as 15-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) which show delayed myocardial clearance, thus permitting single-photon emission tomographic imaging. Interest in the use of BMIPP and similar agents results from the differences which have often been observed in various types of heart disease between regional myocardial uptake patterns of [123I]BMIPP and flow tracer distribution. Although the physiological basis is not completely understood, differences between regional fatty acid and flow tracer distribution may reflect alterations in important parameters of metabolism which can be useful for patient management or therapy planning. These tracers may also represent unique metabolic probes for correlation of energy substrate metabolism with regional myocardial viability. The two agents currently most widely used clinically are 123I-labelled IPPA and BMIPP. While [123I]IPPA is commercially available as a radiopharmaceutical in Europe (Cygne) and Canada (Nordion), multicenter trials are in progress in the United States as a prelude to approval for broad use. [123I]BMIPP was recently introduced as Cardiodine for commercial distribution in Japan (Nihon Medi-Physics, Inc.). [123I]BMIPP is also being used in clinical studies on an institutional approval basis at several institutions in Europe and the United States. In this review, the development of a variety of radioiodinated fatty acids is discussed. The results of clinical trials with [123I]IPPA and [123I]BMIPP are discussed in detail, as are the future prospects for fatty acid imaging.

Animals↗
PubMed1995

[166Dy]dysprosium/[166Ho]holmium in vivo generator.

A novel approach for the delivery of 166Ho (t1/2 = 26.6 h) to tissue is via the in vivo decay of its 81.5 h parent, 166Dy-an in vivo generator system. A critical question for the in vivo 166Dy/166Ho generator system is whether translocation of the daughter nucleus occurs. The in vitro and in vivo integrity of the [166Dy]Dy/166Ho-DTPA complex was investigated and results indicated that no translocation of the daughter nucleus occurs subsequent to beta- decay of 166Dy. Biodistribution studies of [166Dy]Dy-DTPA showed that the ratio of 166Dy/166Ho in bone remains constant (+/- 7%) over a 20 h period, indicating no significant in vivo loss of 166Ho from the complex. Increasing the in vivo residence time of [166Dy]Dy-DTPA complex attached to HSA gave similar results.

Animals↗
PubMed1995

Cardiac SPECT with iodine-123-labeled fatty acids: evaluation of myocardial viability with BMIPP.

The use of 123I-labeled fatty acids is witnessing a resurgence of interest, primarily because of data from recent clinical protocols comparing regional myocardial uptake of 123I-labeled 15-(p-iodophenyl)-3-(R,S)-methylpentandecanoic acid (BMIPP) with flow tracers. Comparison of mismatches in BMIPP and flow tracer distribution (BMIPP < flow tracer) has demonstrated the usefulness of evaluating myocardial viability with BMIPP. BMIPP was introduced in 1993 as "Cardiodine" as an approved radiopharmaceutical in Japan by Nihon Medi-Physics, Inc. This article reviews the clinical use of BMIPP in the assessment of cardiomyopathy, myocardial infarction, ischemic heart disease and for the evaluation of myocardial viability in comparison with PET tracers. The results of two specific protocols demonstrating the utility of using BMIPP to detect viable myocardium are described in detail. The first study compares BMIPP and sestamibi uptake to wall motion and inotropic reserve after acute myocardial infarction in conjunction with two-dimensional echocardiography and low-dose dobutamine stimulation. The second example describes results of a triple SPECT technique using BMIPP reinjection for the assessment of ischemia.

Cardiomyopathies↗